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Characterizing the genomic variation and population dynamics of Plasmodium falciparum malaria parasites in and around Lake Victoria, Kenya
No full textCharacterising the genomic variation and population dynamics of Plasmodium falciparum parasites in high transmission regions of Sub-Saharan Africa is crucial to the long-term efficacy of regional malaria elimination campaigns and eradication. Whole-genome sequencing (WGS) technologies can contribute towards understanding the epidemiology and structural variation landscape of P. falciparum populations, including those within the Lake Victoria basin, a region of intense transmission. Here we provide a baseline assessment of the genomic diversity of P. falciparum isolates in the Lake region of Kenya, which has sparse genetic data. Lake region isolates are placed within the context of African-wide populations using Illumina WGS data and population genomic analyses. Our analysis revealed that P. falciparum isolates from Lake Victoria form a cluster within the East African parasite population. These isolates also appear to have distinct ancestral origins, containing genome-wide signatures from both Central and East African lineages. Known drug resistance biomarkers were observed at similar frequencies to those of East African parasite populations, including the S160N/T mutation in the pfap2mu gene, which has been associated with delayed clearance by artemisinin-based combination therapy. Overall, our work provides a first assessment of P. falciparum genetic diversity within the Lake Victoria basin, a region targeting malaria elimination.AO is supported by a Nagasaki University—LSHTM PhD studentship funded by the WISE programme of MEXT. SC is funded by the Medical Research Council UK (Grant No. MR/M01360X/1) and BBSRC UK (BB/R013063/1). AK received support from JSPS KAKENHI (Grant Nos. JP18KK0248 and JP19H01080) and JICA/AMED joint research project (SATREPS) (Grant No. 20JM0110020H0002). OK received support from JSPS KAKENHI JP19KK0220, Japan. JG received support from a Tackling Infectious Burden in Africa (TIBA) fellowship, the African Academy of Sciences, and the Japan Society for Promotion of Sciences. TGC is supported by the Medical Research Council UK (Grant Nos. MR/K000551/1, MR/M01360X/1, MR/N010469/1, MR/R020973/1) and BBSRC (BB/R013063/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
The electronic effect of quinoline moieties on the lability of platinum(II) complexes of tridentate N^N^N and N^C^N ligands: a kinetic, mechanistic and theoretical analysis
No full textThe rate of the chloride ligand displacement by three thiourea neutral nucleophiles (Nu) of different steric demands, namely thiourea (Tu), N,N’-dimethylthiourea (Dmtu) and N,N,N,’N-tetramethylthiourea (Tmtu) in the complex 2,6-bis(8-quinolyl)-pyridine chloroplatinum(II) (Pt3), was investigated under pseudo-first-order conditions as a function of concentration and temperature using UV–visible spectrophotometry and compared with the literature data of complexes: 2,6-bis(2-pyridyl)pyridine chloroplatinum(II) (Pt1), 1,3-bis(pyridyl)phenyl chloroplatinum(II) (Pt2) and 1,3-bis(8-quinolyl)phenyl chloroplatinum(II) (Pt4). The observed pseudo-first-order rate constants for substitution reactions obeyed the simple rate law
. The results demonstrated that the lability of the chloride ligand is dependent on the degree of synergy between electronic character and the planarity of architectural frame work of the ligands around the platinum centre. The second-order kinetics and large negative activation entropies (ΔS#) assert an associative mode of activation. DFT calculations were performed to support the interpretation and discussion of the experimental data.
Graphic abstract
The retardation in lability of quinoline systems; 2,6-bis(8-quinolyl)pyridine chloroplatinum(II) (Pt3) and 1,3-bis(8-quinolyl)phenyl chloroplatinum(II) (Pt4) is attributable to cis σ-donor effect and twisting of the quinoline rings that offsets the π-acceptor ability on the extended π-system. Conversely, high reactivity of pyridine systems; 2,6-bis(2-pyridyl)pyridine chloroplatinum(II) (Pt1) and 1,3-bis(pyridyl)phenyl chloroplatinum(II) (Pt2), is due to their rigid planar structure that facilitates effective π-acceptor ability.The authors are gratefully indebted to the University of KwaZulu-Natal and the National Research Foundation (NRF, South Africa) for bursary to I.M. Wekesa and financial support
Understanding the role of flexible alkyl-α,ω-diamine linkers on the substitution behaviour of dinuclear trans-platinum(II) complexes: A kinetic and mechanistic study
No full textAn investigation of the role of flexible alkyl-α,ω-diamine linkers on the substitution behaviour of dinuclear trans-platinum(II) complexes. The substitution reactions of four dinuclear trans-platinum(II) complexes viz. [PtNH3Cl2]2-µ-NH2(CH2)2NH2] (P12), [PtNH3Cl2]2-µ-NH2(CH2)3NH2] (P13), [PtNH3Cl2]2-µ-NH2(CH2)4NH2] (P14) and [PtNH3Cl2]2-µ-NH2(CH2)5NH2] (P15) with three neutral thiourea-based nucleophiles specifically: thiourea (TU), N-methyl-2-thiourea (MTU) and N,N-dimethyl-2-thiourea (DMTU) were studied quantitatively under pseudo-first-order condition as function of concentration and temperature by conventional UV–Visible and stopped-flow spectrophotometers. The ligand substitution reaction of the complexes proceeds in veritably three consecutive steps. Each step follows first-order kinetics with the respective complex and nucleophile. The pseudo first order rate constants, kobs(1/2/3), for sequential substitution of the chlorido ligands, the ammine, and subsequent displacement of the linker obeyed the rate law: kobs(1/2/3) = k(1/2/3)[NU]. The ligand substitution reactions were driven by both electronic and steric factors. However, our findings revealed that upon the substitution of the chlorido ligands by the nucleophiles at the platinum centres, the σ-donor capacity via inductive effect of these electron-rich nucleophiles over compensate the steric strain imposed by the nucleophiles and by the alkanediamine linker at the substitution sites. Consequently, electronic factors governed the overall reaction pattern of these complexes. 195Pt NMR results confirmed the simultaneous substitution of all the chlorido ligands by thiourea-based nucleophiles, followed by the subsequent but successive displacement of the ammine groups and the flexible alkanediamine linker from the metal centres. The order of reactivity of the nucleophiles with the complexes decreases with the increase in steric bulk in the nucleophiles: TU > MTU > DMTU. The small positive enthalpy and the large but negative entropy confirm the associative mode of activation for all the studied complexes. Computational modelling using density functional theory (DFT) calculations was employed to rationalise the kinetic trends
Antimicrobial activities of uvariodendron anisatum fractions
No full textConventional antimicrobial agents available for treating infections caused by microorganisms pose a wide range of challenges which include antimicrobial resistance & severe side effects. In an attempt to develop potent drugs for the treatment of infectious diseases, antimicrobial agents in natural products have been widely researched. This research project aimed at establishing the antimicrobial effects of Uvariodendron anisatum Fractions .The Fractions were obtained through column chromatography from Uvariodendron anisatum root extract which was prepared by maceration. Antibacterial activity against Escherichia coli & Staphylococcus aureus was investigated via disk diffusion method. Results obtained did indicate that the Fractions possess antibacterial activity. It can therefore be concluded that the root extracts of Uvariodendron anisatum have Fractions of great ethno medical importance & can be used for treatment of infections caused by Escherichia coli & Staphylococcus aureus.It is thus recommended that bioassay guided techniques be utilized in search of the active extracts from this plant. Furthermore, there is need to establish profiles of in vivo antibacterial effects of the isolated Fractions
Association between Metabolic Syndrome and Substance Dependence: A Cross-sectional Study in Kenya
No full textMetabolic syndrome and its defining components remain an understudied area of human health research in Kenya and Africa. Understanding the relationship between substance dependence and the occurrence of metabolic syndrome is critical in prevention and clinical management of the related complications.
Methods: This was a cross-sectional study in 6 rehabilitative centers in 3 counties in Kenya with a conveniently selected sample size of 166 participants. A signed informed consent was obtained from each participant following which anthropometric and biochemical measurements were obtained. Descriptive statistics and chi-square test were used to describe the prevalence of metabolic syndrome and the relationship of the defining criteria with the substance of dependence.
Results: A quarter of the respondents were overweight and 6% obese. Fasting blood glucose was elevated in 62% of the sampled population with triglycerides having a significant variation with a mean of 216.95mg/dl and a standard deviation of 151.107. A prevalence rate of 4.8% was established based on the Harmonized Joint Scientific Statement on Metabolic syndrome for the African region. 87.34% of the population showed at least one elevated defining criteria with alcohol as the most prevalent substance of dependence. There was statistical difference of fasting blood glucose and triglycerides with alcohol use.
Conclusion: The findings indicate that alcohol use resulted to elevated levels of fasting blood glucose and triglycerides. There is need for emphasis on a multidisciplinary approach to substance dependence and metabolic syndrome management integrating physical activity interventions, dietary modifications and psychotherapeutic approaches
Determinants of perceptions on nursing care among cancer patients admitted in oncology wards at Kenyatta National Hospital, Nairobi County, Kenya.
No full textNursing care is meeting both physical and psychosocial needs of patients. Cancer patients experience more biopsychosocial needs than other patients, hence they require more nursing care. An oncology nurse therefore provides physical, psychosocial and spiritual care to cancer patients. The purpose of this study was to assess the determinants of perceptions on nursing care among cancer patients admitted in oncology wards. The research objectives were to determine cancer patient characteristics that influence their perceptions on nursing care, determine cancer patient expectations on nursing care and lastly cancer patient satisfaction with the nursing care provided while in the ward. The study design was descriptive cross-sectional, using quantitative approach. The sample size was 91 patients who were selected using purposive sampling technique. The target were adult patients (both males and females) aged 18 years and above admitted in oncology wards at KNH (GFD and 8C), with a confirmed diagnosis of cancer and who had received care for at least 48 hours. Data collection tool was a standardised researcher administered, semi structured questionnaire and Likert scale in English and Kiswahili version. This tool was adopted from the caring assessment questionnaire (care-Q) by Larson, and modified as per research objectives and literature review. The tool was pretested in Nakuru PGH. Data was analysed using SPSS version 21 using both descriptive and inferential statistics. Ethical clearance was obtained from MKU, and KNH-UoN ERC, Permit from NACOSTI. Participation in the study was voluntary. Residence and hospital length of stay affected positively the perception on nursing care at p =0.022 and p=0.004 respectively. Cancer Patients, 92.3% (84) had high expectations on nursing care. There was a significant association between patient expectation with perception on physical nursing care, p=0.028. 53.8% of the patients were not satisfied with psychosocial care with 97.8% (89) having their expectations on psychosocial care partially met. A high score, 97.8% (89) of the cancer patients identified emotional support as the priority psychosocial need, with 82.4% (75). Majority (76.5%) had a neutral position with regard to satisfaction status with physical care. Treatment was rated as a priority physical need by most patients (37.4 %= 34). Majority, 52.7% (48) recommended assessment of patient needs to improve physical care. A higher percentage, 59.3% (54) felt both psychosocial care and physical care were important. Generally, 94.5% (88) were satisfied with care in the ward with 96.7% (84) reporting that physical care was most satisfying. In conclusion, cancer patients’ characteristics, expectations, and satisfaction with nursing care had a positive association with their perceptions on nursing care offered in the ward. Psychosocial care was less satisfying to the cancer patients. The researcher recommends that oncology nurses should be keen to meet all patient needs to promote care satisfaction with emphasis to psychosocial care.
Identification of Novel Malaria Transmission-Blocking Vaccine Candidates
No full textControl measures have significantly reduced malaria morbidity and mortality in the last two decades; however, the downward trends have stalled and have become complicated by the emergence of COVID-19. Significant efforts have been made to develop malaria vaccines, but currently only the RTS,S/AS01 vaccine against Plasmodium falciparum has been recommended by the WHO, for widespread use among children in sub-Saharan Africa. The efficacy of RTS,S/AS01 is modest, and therefore the development of more efficacious vaccines is still needed. In addition, the development of transmission-blocking vaccines (TBVs) to reduce the parasite transmission from humans to mosquitoes is required toward the goal of malaria elimination. Few TBVs have reached clinical development, and challenges include low immunogenicity or high reactogenicity in humans. Therefore, novel approaches to accelerate TBV research and development are urgently needed, especially novel TBV candidate discovery. In this mini review we summarize the progress in TBV research and development, novel TBV candidate discovery, and discuss how to accelerate novel TBV candidate discovery
Evaluation of antibacterial activity of Phytexponent preparation on selected priority Bacterial strains at higher concentrations
Get PDFH. influenzae, A. baumanii and S. enteritidis are pathogenic micro-organisms
known to cause disease in human beings. They have developed resistant strains
over the years thus made it difficult to treat these bacterial infections. They are part
of the list of pathogens published by WHO that urgently need new antibiotics. Thus,
this study aims to find an alternative to the conventional antibiotics in which the
bacterial strains have developed resistance. Antibiotic resistance brings about
treatment failure, increased cost of treatment due to prolonged hospitalization and
use of expensive antibiotics. The conventional antibiotics are also known for their
side effects which lead to non-compliance in most patients thus increasing the rate
of development of resistance. The evaluation of antibacterial activity of plant
sources has increased in order to come up with alternatives for the treatment of
bacterial infection. PhytExponent is a poly-herbal preparation with five herbs that have
shown to have significant in vitro antibacterial activity. The disc diffusion assay
technique is an example of agar diffusion method used for susceptibility testing and
assay for potency. It is the most used technique in most microbiology laboratories
to test for susceptible micro-organism to certain antibacterial agents. Using the disc
diffusion technique, PhytExponent demonstrated increased antibacterial activity
against the test micro-organisms as its concentration increased
Analysis of relationship between entrepreneurship education practices and entrepreneurial intention of technical vocational education and training students in Kenya
No full textThe study analyzed relationship between entrepreneurship education practices and entrepreneurial intention of Technical and Vocational Education and Training students in Kenya. Succeeding specific objectives were considered. To determine effect of entrepreneurship training content on entrepreneurial intention of Technical and Vocational Education and Training students in Kenya, find out effect of entrepreneurship pedagogies on entrepreneurial intention of Technical Vocational Education and Training Students in Kenya, assess effect of trainer attributes on entrepreneurial intention of Technical and Vocational Education and Training students in Kenya and to determine if family orientation moderates relationship between entrepreneurship education practices and entrepreneurial intention of the reference group. Positivism research philosophy and explanatory research design approaches were used. Using stratified simple random sampling supported by key informer interviews. Data was collected through questionnaires and interviews from 365 respondents covering final year students, entrepreneurship trainers and management of public technical training institutions located in Nairobi and Kajiado Counties as at July 2018. Results from reliability analysis indicated a Cronbach alpha above 0.7 for all items thus reliable. Descriptive and inferential statistical tools of mean, standard deviation, percentage, correlation and linear regression model was utilized to analyze. The study used p-values and the t-statistic values to test hypothesis. Results were presented in narrative, graphs and tables. Results of hypothesis testing revealed a strong positive significant relationship between entrepreneurship education content (p=0.0000.05, and entrepreneurial intention of the referenced group. The moderation results showed that family orientation did not have moderating effect on the relationship between the independent variables and the dependent variable. The study thus concluded that entrepreneurship education content, entrepreneurship pedagogies, trainer attributes and learning resources can be used as predictors of entrepreneurial intention of Technical Vocational Education and Training students in Kenya. Study will benefit government, curriculum developer, researchers and management of Technical and Vocational Education and Training Institutions. A multi-agency approach and collaboration in implementation and management of entrepreneurship education was recommended. There is need for stakeholders to undertake holistic intentional measures aimed at strengthening entrepreneurship education practices. In addition, further study may be undertaken to establish percentage of Technical and Vocational Education and Training students who actualize their entrepreneurial intention into entrepreneurial action
The effect of substituents on the reactivity of dichloridotriphenylphosphinoruthenium(II) complexes: kinetic and mechanistic study
No full textThe rates of substitution of chloro ligands from a series of ruthenium(II) complexes, [Ru(κ3-L)(PPh3)Cl2] (L = 2,2′:6′,2′′-terpyridine, 1; 4′-(4-methylphenyl)-2,2′:6′,2′′-terpyridine, 2; 4,4′4″-tri-tert-butyl-2,2′:6′,2′′-terpyridine, 3; 4′-(4-chlorophenyl)-2,2′:6′,2′′-terpyridine, 4; 4-chloro-2,2′:6′,2′′-terpyridine, 5 and 2,6-bis(2-pyrazolyl)pyridine, 6), by thiourea nucleophiles was investigated under pseudo-first-order conditions in methanol as a function of nucleophile concentration and temperature. The chloro ligands were substituted in two steps and the reactivity trend was 4 > 5 > 2 > 1 > 6. Complexes 2 and 3 having donor substituents on the 2,2′:6′,2′′-terpyridine backbone experience a trans-effect making them more reactive than 1. Complexes 4 and 5 are more reactive than 1 due to enhanced π-back-bonding brought about by electron-withdrawing substituents on their 2,2′:6′,2′′-terpyridine backbones. The reactivity of 4 is higher than 5 due to greater electron acceptor-ability of the chlorophenyl substituent than the chloro substituent in 5. The 2,6-bis(pyrazolyl)pyridine ligand in 6 retards the reactivity of the complex compared to 1 due to the cis-donor effect of the pyrazole. The reactivity of the complexes is associative for all nucleophiles in step one and only thiourea in step two. The substitution reactions proceed by a steady changeover from an associative interchange mechanism (Ia) to a dissociative interchange (Id) mechanism on increasing steric hindrance.This research was funded by the University of KwaZulu Natal South Africa